During Segmental Liver Resection Project Summary/Abstract Liver resection is usually performed for the removal of either benign or malignant tumors. A major issue for the liver surgeon is control of bleeding during parenchymal transection;due to the liver's unique dual blood supply and extensive collateral flow, bleeding from the cut surface of the liver can be problematic. Current techniques for liver parenchymal transection cannot adequately control bleeding from larger vessels. The Pringle maneuver (occlusion of the entire porta-hepatis) minimizes bleeding but exposes the entire liver to ischemic injury. To avoid this, surgeons perform "anatomic" resection;the major vessels to half of the liver are ligated and divided, sacrificing large volumes of "normal" liver and placing the patient at risk for inadequate liver volume. "Non-anatomic" or "segmental" resection can be performed for tumors near the periphery, but significant bleeding can be encountered since blood flow to the targeted tissue cannot be controlled. The deleterious effects of hemorrhage during malignant liver resection are not only increased morbidity and mortality directly related to blood loss, but also increased recurrence rate, shortened disease-free interval and decreased life expectancy accompanying major peri-operative blood replacement. This proposal describes a technique to achieve bloodless surgery and reduce the risk of hemorrhage while minimizing warm ischemia to the organ. This technique will support the adoption of minimally invasive laparoscopic and robotic techniques. Pluromed has developed aqueous, biocompatible Rapid Transition Polymers" (RTP's") that exist in a liquid state at low temperatures but quickly transition to gel near body temperature. This phase change is fully reversible by cooling and the polymer cannot re-solidify once dissolved. The polymer is being used clinically in Europe for temporary vascular occlusion in coronary and peripheral bypass surgery. Pre-clinical work in the porcine kidney has demonstrated the ability to temporarily interrupt flow to only the renal tissue destined for resection, allowing bloodless surgery while maintaining normal flow to the uninvolved portion of the kidney. The complexity of the liver's circulation mandates study of this technique for hepatic resection. The Overall Aim is to optimize the technique to achieve vascular inflow control, improving the ease and safety of segmental liver resection. This will be achieved with in vitro and in vivo experiments in large animals. The Specific Aims are: 1. Optimize the polymer properties and injection techniques to achieve temporary occlusion in the liver. 2. Achieve temporary targeted occlusion and reperfusion in the living porcine liver. 3. Further characterization of temporary targeted occlusion and reperfusion of liver segment 5. 4. Assess the efficacy of temporary targeted occlusion for segmental liver resection. 5. Compare liver resection with and without the use of RTP's in chronic survival experiments. Phase I will demonstrate RTP's ability to facilitate segmental liver resection. Phase II will then expand this technology to the remainder of the liver and to the use of RTP's with minimally invasive techniques. Importantly, this technique is relevant to many applications and the proposed work will serve as a paradigm for the use of RTP's in other complex, highly vascularized organs such as the lungs and spleen. PUBLIC HEALTH RELEVANCE: The number of liver resections is increasing primarily due to the improved survival of cancer patients with liver metastases, yet despite the 120,000 hepatic resections performed each year in the U.S., this remains a significant and somewhat risky operation with hemorrhage as the primary risk. Current techniques for liver transection cannot adequately control bleeding from larger vessels;either the entire liver is subjected to ischemic injury or large areas of "normal" liver are sacrificed. "Segmental" resection can be performed, where the resected segment is limited to the tumor and an acceptable margin, but a technique is needed to achieve temporary interruption of flow to only the targeted segment, while allowing normal flow to the remainder of the organ. Additionally, this technique's ability to provide a bloodless field would support the adoption of minimally invasive laparoscopic and robotic liver surgery. This application proposes optimization of such a technique.